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dc.contributor.advisorMcLellan, Alexander
dc.contributor.authorMuhsin, Morad-Remy
dc.date.available2012-12-09T19:46:09Z
dc.date.copyright2012
dc.identifier.citationMuhsin, M.-R. (2012). The Interface of Metastatic Tumours and the Immune System (Thesis, Bachelor of Biomedical Sciences with Honours). University of Otago. Retrieved from http://hdl.handle.net/10523/2660en
dc.identifier.urihttp://hdl.handle.net/10523/2660
dc.description.abstractPrimary tumours are rarely lethal; instead most cancer deaths are due to the spreading of the tumour to other sites in the body (metastasis). One major pathway of metastatic disease is the migration of tumour cells from the primary tumour to the draining lymph node. In this study, we examined the interaction of tumour cells and their apoptotic vesicles (ApoV) with CD169+ macrophages within the subcapsular sinus of the lymph node using CD169-/- mice. As previously shown by our laboratory, lymphoma-derived microvesicles bind to the CD169 receptor expressed by macrophages. In this study, we have successfully confirmed the binding of melanoma-derived ApoV by CD169. We then established lymph node metastatic models of B16 melanoma using forelimb, ear, and skin tumour implantation. In addition, we have attempted a novel flank abrasion method developed by Dr. Jason Waithman (Telethon Institute for Child Health Research, Australia). We next addressed the importance of CD169-macrophage lymph node barriers on tumour spread and the impact of metastatic disease in the lymph node on the immune response against tumours. Strikingly, tumour progression within the draining lymph node was significantly lower in CD169-/- mice compared to wild-type mice. However, this finding was confined only to our murine subcutaneous melanoma model, and not the intravenous lung metastases model. Furthermore, we investigated the effects of melanoma-derived ApoV on the lung tumour progression. Interestingly, pretreatment of mice with tumour ApoV significantly increased the number of metastatic foci on lungs. This suggests that chemotherapy of tumours may cause the release of ApoV as pro-metastatic agents. To our knowledge, this is the first report of apoptotic cell products enhancing tumour metastasis. Therefore our results provide an important starting point to understand the role of CD169 and tumour vesicles in the anti-tumour response and in preventing metastatic disease.
dc.format.mimetypeapplication/pdf
dc.language.isoen
dc.publisherUniversity of Otago
dc.rightsAll items in OUR Archive are provided for private study and research purposes and are protected by copyright with all rights reserved unless otherwise indicated.
dc.subjectMetastatic tumours
dc.subjectMetastases
dc.subjectTumour
dc.subjectImmunotherapy
dc.subjectTumour vesicles
dc.subjectMelanoma
dc.titleThe Interface of Metastatic Tumours and the Immune System
dc.typeThesis
dc.date.updated2012-12-07T04:39:12Z
dc.language.rfc3066en
thesis.degree.disciplineMicrobiology & Immunology
thesis.degree.nameBachelor of Biomedical Sciences with Honours
thesis.degree.grantorUniversity of Otago
thesis.degree.levelHonours
otago.openaccessOpen
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